Dry powder inhalers such as those described in U.S. Pat. Nos. 7,305,986, 7,464,706 and U.S. patent application Ser. No. 12/484,129 (2009/0308391), which disclosure is incorporated herein by reference in their entirety, can generate primary drug particles or suitable inhalation plumes during an inspiratory maneuver by deagglomerating the powder formulation within a capsule or a cartridge. Dosing reproducibility requires that the drug formulation is uniform and that the dose can be delivered to the patient with consistent and reproducible results. Therefore, the dosing system must operate to completely discharge all of the formulation effectively during an inspiratory maneuver when the patient is taking his/her dose. The benefits of delivering drugs via the pulmonary circulation are numerous and include, rapid absorption into the arterial circulation, avoidance of drug degradation by liver metabolism, ease of use, i.e., lack of discomfort of administration, such as discomfort encountered by other routes of administration, for example, by subcutaneous and intravenous injections.
The consistency in drug delivery from an inhaler is due in part to the consistency in resistance to air flow within the air passages of the inhalation device. High resistance dry powder inhalers such as those disclosed in U.S. Pat. Nos. 7,305,986 and 7,464,706, and U.S. patent application Ser. No. 12/484,129 (2009/0308391), deliver drug formulations in a consistent manner. One of the parameters used to ascertain or predict if an inhaler would deliver a dose with consistency during use is the resistance to air flow of the device, which is due in part to the internal geometries of the air conduits. Another parameter related to dosing consistency is the quality of the powder plume generated from the inhaler during use, which is dependent on various factors, for example, the type of dry powder and the inhaler system's ability to deagglomerate the powder into fine particles that can reach the lungs during an inhalation.
Present systems and methods for measuring particle distribution are commercially available, however, the commercial apparatuses are targeted to be used for relatively lower resistance inhalers. For example, in one standard method, an inhaler module uses laser diffraction technology to quantify particle size distribution in dry powder inhalers (DPI). The standard inhaler module is comprised of a chamber in which the inhaler is mounted outside in ambient air and the plume travels through an enclosed chamber. The plume is formed by a vacuum generated across the chamber and powder flows through the device. Midway through the chamber, the powder plume travels through the zone in which the laser is projected thus causing the laser beam to diffract after colliding with the particles. A collection of sensors across from the laser source measure these diffraction patterns and, using Mie theory (an analytical solution of equations for the scattering of electromagnetic radiation by spherical particles), interpret them to quantify particle size distribution of the inhaler powder discharge in the plume. In use, the vacuum can generate areas of high and low pressure within the chamber, creating a non-uniform plume.
In this standard set up, the way in which the plume moves through the chamber will affect the system's ability to accurately quantify the particle size distribution of the powder plume. For instance, the plume residence time in the chamber is critical to accurate measurement. Ideally, the system should be able to measure the plume in real time. For example, if the plume is discharged over a time interval of 0.5 seconds, the standard system should be able to detect and measure the plume in approximately 0.5 seconds.
There are several other parameters that can affect the measurement of the particle size distribution of a plume in a chamber. For example, variations in environmental effects inside the chamber, such as turbulence, certain sized powder particles will spend increased amount of time in the measurement zone. This behavior would cause the particles to be measured multiple times (at least more than once), thus increasing their relative presence within the overall particle size distribution which leads to erroneous representation of actual data.
Additionally, particle size distribution measurements made using prior art systems and relatively small inhalation devices are inconvenient to use and yield erroneous or irreproducible results due to the variations in conditions provided by the chamber, for example, powder deposition in internal surfaces, including the lenses of the adaptor which can result in additional diffractions. Additionally, the adaptor and lenses must be cleaned repeatedly after each use, due to the increased turbulence generated inside the device as described above, all of which can lead to inconsistent measurements of the powder plume.
Therefore, the inventors have seen the need to design and manufacture a simple device for adapting to any laser diffraction apparatus, and a method for measuring particle distribution to ascertain the powder characteristics emitted by an inhaler in use for determining the quality of the powder and effectiveness of the inhaler in dosing a patient.